San Francisco State University

NIH Research Projects · FY 2025 · 2022-08

Abstract Penicillins represent one of the most impactful antibiotics in use for the resolution of gram-positive bacterial infections including bacterial meningitis, diptheria, strep throat, syphilis, gonorrhea, and yaws disease that afflict more than 6 million people annually. These antibiotics are frequently in short supply and improved production methods are needed that both increase the accessibility while reducing inefficiency and environmental impacts associated with current production methods. The primary route to the commercial production of penicillins begins with batch fermentation of the fungus, P. chrysogenum as a biosynthetic route to 6-aminopenicillanic acid (6-APA), which is subsequently used as a starting material for the synthesis of b-lactam antibiotics. As an alternative to currently employed organic synthetic routes to amidation of 6-APA, chemoenzymatic synthetic methods based on the amidation of 6-APA by penicillin amidases (PAs) or isopenicillanic acid transferases (IATs) provide a competitive green chemical approach to penicillin-based antibiotics. Each chemoenzymatic approach poses unique challenges. The amidase-catalyzed acylation of 6-APA requires the use of chemically activated carboxylic acid derivatives as substrates and proceeds with low transformation efficiency. IATs on the other hand are dependent on phenylacetyl- Coenzyme A ligases, which have low stability and limited substrate specificity. In the present work we target an alternate chemoenzymatic strategy for the synthesis of penicillins from aldehydes by joining the activities of IAT and an engineered thiol-acylating aldehyde dehydrogenase (TAD). The first specific aim of this work will target the selective introduction of mutations in the catalytic active site of phenylacetaldehyde dehydrogenase (NPADH) from Pseudomonas putidia (S12), which has a broad aldehyde specificity. Mutations will target the transformation of NPADH into a TAD for the synthesis of the N-acetylcysteamine (SNAc) thioesters. In our second aim, SNAc thiosesters, which are surrogates of acyl-CoA will be introduced with 6- APA co-substrates in the IAT-catalyzed synthesis of penicillins. This strategy is expected to result in a high product yield while eliminating the limitations associated with the phenylacetyl CoA ligases. The development this process will serve as prototypical green-chemistry pathway that can be further expanded into a platform for the production of existing and new classes of b-lactam antibiotics.

NIH Research Projects · FY 2025 · 2022-05

We will take advantage of an avian model system to study viruses that infect malaria parasites. Using a high throughput sequencing approach, we will identify the prevalence of these viruses and their evolutionary history. Results will reveal information about these newly discovered viruses, and ultimately identify new approaches for combating human malaria.

NIH Research Projects · FY 2026 · 2022-04

The goal of the U-RISE program at San Francisco State University (SFSU) is to develop a diverse pool of scientists earning a PhD, who have the skills to successfully transition into careers in the biomedical research workforce. San Francisco State University has dramatically increased the number of underrepresented (UR) undergraduate students from SFSU that enter and succeed in PhD programs in the biomedical sciences during the past 20 years of NIH support. Prior to the NIH funded training programs, only one SFSU UR undergraduate student per decade entered a biomedically relevant PhD program. Today, every year more than 13 undergraduate UR SFSU students are being admitted into top PhD programs. We propose to continue our successes in preparing SFSU U-RISE trainees for PhD programs in the biomedical sciences while embracing the challenges associated with improving and enhancing our research and academic training effectiveness. We will prepare 32 highly qualified underrepresented junior/senior students each year in a rigorous science curriculum and provide them with high quality and stimulating research experiences. We will also provide academic and professional skills activities to enhance competitiveness for PhD programs. To adapt to the rapidly evolving biomedical research training landscape, we plan to continue to enhance these best practices as the foundation for the seminars, workshops, science literacy and communication series, community building, computational skills, and colloquium and honors courses in this new U-RISE program. In the proposed U-RISE program we will focus on 1) improving and enhancing computational and quantitative skills, 2) strengthening writing and science communication skills, and 3) expanding alumni networks and near-peer mentoring. To achieve our overall training goals, we will pursue the following measurable objectives: Objective 1: At least 75% of participants will enter biomedical PhD programs. Objective 2: Ensure that U-RISE trainees are progressing in the research and academic skills training that will enhance 1) success in completing an undergraduate STEM degree and 2) success in PhD programs. Objective 3: Expand our academic and scientific skills training to enhance competitiveness and success in biomedical PhD programs. Specifically, training in computational and quantitative skills, enhancing scientific writing and communication skills, and building a strong near-peer alumni network.

NIH Research Projects · FY 2025 · 2021-09

Deaths from chronic diseases are disproportionately higher in communities of color. This is expected given the well-documented health inequities in the United States caused by centuries-old underinvestment in their wellness. To begin to redress this underinvestment during an economic crisis requires cost-effective, low- resource interventions. It also requires community engagement to ensure uptake and sustainability. Therefore, we propose to undertake community-prioritized research that will engage ancestral knowledges from different communities of color in a multilevel effort to address growing health disparities via intersectoral collaborations. The overall goal of our transformative Reclaiming Nature project is to reduce growing health disparities in Black, Indigenous, and People of Color (BIPOC) communities through examination of culturally-appropriate interventions. These are aimed at reducing embodied stress in transitional-age BIPOC so as to prevent their development of chronic diseases as adults. The development of chronic diseases has been linked to the embodiment of stress through biological processes that include cortisol dysregulation and telomere erosion. In fact, emerging research from several research groups, including our own, finds that erosion of telomere in communities of color is accelerated. This is likely due to racism and discrimination that increase chronic stress and limits access to the social determinants of health (e.g., employment, education, housing). We thus aim to reduce embodied stress through increased access to what can be considered a social determinant of health – equitable access to physical activity in public parks. The proposed work is grounded by the National Institute of Minority Health and Health Disparities (NIMHD) Research Framework, and is enabled by strong partnerships between academic and community researchers, public and private outdoor specialists, and government leaders. They are brought together to extend the work of the Roadmap to Peace initiative. In 2013 this initiative was borne out of a community call to action following the shooting deaths of several Latinx teens. Historically it has aimed to engage youth in healthy and healing relationships, and currently leads “La Cultura Cura” (Culture Heals) efforts to engage BIPOC youth (through racial/ethnic sister initiatives) in healthy and healing relationships with, and within, nature. This aligns with the efforts of partnering outdoor specialists to increase park visits by BIPOC communities, and with the research focus for the proposed work. Thus, a key innovation of the proposed work is a community-prioritized, intersectoral, multilevel approach for implementing and testing a healing intervention in nature by insider researchers committed to building sustainable systems change. The insider researchers come from the communities being recruited to the intervention. They are committed to examining the culture of four different communities (Black, Latinx, Pilipinx, and Pacific Islander) to test and institutionalize ideas for systems change as part of transformative research for health equity.

NIH Research Projects · FY 2025 · 2021-08

The goal of the Bridges to the Doctorate Research Training Program at San Francisco State University (SFSU) (“Bridge Program”) is to develop a diverse pool of scientists earning a Ph.D., who have the skills to successfully transition into careers in the biomedical research workforce. SFSU and the University of California, San Francisco (UCSF) have developed a cooperative graduate program to increase the number of under-represented (UR) students that pursue biomedical research careers. This Program will provide UR students (primarily Biology and Biochemistry) with a quality and focused master's degree education at SFSU that prepares them to be competitive for acceptance into top-ranked biomedical science doctoral programs such as UCSF. The objectives are to: 1) engage all Bridge trainees in research activities, 2) provide the scientific literacy to ensure the successful completion of M.S. and Ph.D. degrees in a timely manner, and 3) ensure the transition of Bridge trainees to Ph.D. programs. These objectives will be successfully met through the combination of (i) close and careful academic and research advising by peers, preceptors, course instructors and PDs, (ii) a nurturing and productive research experience with Bridge preceptors, (iii) registration in two courses (“Strategies for Success” and “Science Coding Immersion Program (SCIP)”) that provide professional development to improve quantitative, writing, and oral communication skills while building community, and (iv) role modeling from established UR scientists in our formal Speaker Series. The M.S. program is divided into 4 semesters, with a unique “Strategies for Success” each semester, and the “SCIP” course in the summer between 1st and 2nd year. The “Strategies” course develops writing and oral communication skills through development of the IDP, statement of purpose, abstract writing, presentations and mock interviews. Ph.D. preparation includes informational sessions on Ph.D. programs, and PhD/career panels led by SFSU alumni. These courses also cover RCR and rigor and reproducibility, over 2 semesters. SCIP develops community through coding lessons, with biologically-relevant data sets. Over the last 15 years, 175 previously funded M.S. students have completed Ph.D. programs, with another 75 pending (anticipated completion dates between 2021- 2025). Over the last 5 years alone, an average of 22.4 students have entered Ph.D. programs yearly, with an average of 3.6 entering UCSF Ph.D. programs (2, 2, 4, 3 and 7 entering from 2016- 2020). This proposal therefore requests funding for 32 MS students (16 first year and 16 second year), to maintain the strong success of the combined NIH Bridge and RISE programs previously in existence at SFSU.

NIH Research Projects · FY 2026 · 2019-08

PROJECT SUMMARY/ABSTRACT Polyamines and the enzymes that regulate them are critical for numerous cellular processes in all domains of life. These molecules are flexible, positively charged, and can be used to modify proteins, bacterial cell wall polysaccharides, aid antibiotic resistance, and act as scaffolds to create new molecules like siderophores and toxins. They help control expression of different genes during stressful situations, and they are often signals for bacterial biofilms or indicators for problems in human health. Polyamine acetyltransferases (PAATs) serve to partially neutralize the charges of these molecules, but we are beginning to find new ways these enzymes are being regulated and function in different organisms. My laboratory studies these PAAT enzymes and tries to understand how they look and how they work from structural, functional, and regulatory perspectives in different bacterial pathogens and other non-pathogenic organisms. Based on our work in the previous funding period, we have identified new avenues for exploring these properties of PAATs. We envision building on our previous work to expand our fundamental knowledge in the field and address the following questions during the next funding period: 1) Which sequence and/or structural attributes contribute to PAAT substrate specificity and oligomerization?, 2) Which PAAT residues dictate polyamine acceptor substrate and acyl donor substrate specificity, and 3) How are PAAT proteins regulated? The results of these studies will help establish key sites on bacterial PAATs that can be targeted for drug development that are not redundant in human homologs and help us more fully understand the fundamental roles these enzymes play in a variety of cellular processes and communities.